Opposing patterns of abnormal D1 and D2 receptor dependent cortico-striatal plasticity explain increased risk taking in patients with DYT1 dystonia

Abstract

AbstractPatients with dystonia caused by the mutated TOR1A gene exhibit a risk neutral behaviour compared to controls who are risk averse in the same reinforcement learning task. We hypothesised this increased risk taking could be reproduced by a reinforcement learning model which included biologically realistic striatal plasticity learning rules. We aimed to test whether a specific combination of cortico-striatal plasticity abnormalities at D1 and D2 receptors could explain the abnormal behaviour. We found a model of cortico-striatal plasticity could generate simulated behaviour indistinguishable from patients only when both D1 and D2 plasticity was abnormally increased in opposite directions: specifically when D1 synaptic potentiation and D2 depotentiation were both increased. This result is consistent with previous observations in rodent models of cortico-striatal plasticity at D1 receptors, but contrasts with the pattern reported in vitro for D2 synapses. This suggests that additional factors in patients who manifest motor symptoms may lead to divergent effects on D2 synaptic plasticity that are not apparent in rodent models of this disease.